The effect of gestational diabetes mellitus on pregnancy outcomes in advanced primiparous women: A retrospective study

Gestational diabetes mellitus (GDM) could have a variable degree of adverse effects on pregnancy outcomes for both pregnant women and newborns. The purpose of the study was to explore the effect of GDM on pregnancy outcomes in advanced primiparous women. A total of 1076 advanced primiparous women were included between January 2020 and December 2022. All these women were divided into the GDM group (n = 434) and the non-GDM group (n = 642). Variables included baseline characteristics, maternal, and newborn outcomes were collected. The risk of each adverse outcome was analyzed by multivariate logistic regression models. The effect of blood glucose control on pregnancy outcomes was further analyzed among GDM women with good glycaemic control (n = 381) and poor glycaemic control (n = 53). Analysis of baseline characteristics demonstrated a significant difference in prepregnancy body mass index (median, IQR: 22.27 [20.58–24.44] vs 21.17 [19.53–22.86], P < .01) between the GDM group and the non-GDM group. A significantly higher incidence rate of adverse pregnancy outcomes was found in advanced primiparous women with GDM, such as polyhydramniosis, premature birth, low-birth weight, macrosomia, and neonatal intensive care unit admission (all P < .05). Compared with the non-GDM group, the risk of polyhydramniosis was nearly twice as high in the GDM group (adjusted odds ratio: 1.94, 95% confidence interval: 1.01–3.72, P = .04) after adjusted baseline characteristics. Among the GDM group, the women with poor glycaemic control showed a significantly higher incidence rate of polyhydramnios, hypertensive disorders of pregnancy, cesarean delivery, premature birth, low-birth weight, macrosomia, and neonatal intensive care unit admission was significant than the women with good glycaemic control (all P < .05). GDM was an independent risk factor for polyhydramnios in advanced primiparous women. At the same time, good glycaemic control in diabetics advanced primiparous women could reduce adverse pregnancy outcomes.


Introduction
With the rapid socio-economic development of China, the change in the concept of marriage, and the quest for quality of life, there has been an increasing trend in the number of elderly first-time mothers in China annually.Advanced maternal age (AMA) is commonly defined as maternal age ≥ 35. [1]AMA carries reduced fertility, increased demand for assisted reproductive techniques (ART), and an ascending early miscarriage due to having impacts on chromosomal and genetic disorders.During pregnancy, AMA also increases the probability of pregnancy complications, including gestational diabetes mellitus (GDM), fetal growth restriction, stillbirth related, hypertension, preterm birth, disorders of pregnancy, and so forth. [2]Furthermore, the incidence of GDM in women with AMA has been dramatically increasing. [3,4]GDM is a common complication of pregnancy, defined as defined as abnormal glucose tolerance occurring or first detected during pregnancy and without a history of diabetes. [5]A systematic review and meta-analysis by Ye et al [6] demonstrated that GDM had variable adverse effects on The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.Supplemental Digital Content is available for this article.pregnancy outcomes in the near and distant future, including the higher incidence of gestational hypertension, cesarean section rate, macrosomia, postpartum hemorrhage, preterm birth, transferred to neonatal intensive care unit (NICU) admission.Compared with women without GDM, the risk for developing type 2 diabetes mellitus (T2DM) was 7.5 times in women with GDM, and their offspring were more likely to develop childhood obesity and T2DM. [7]A previous study reported that good glycaemic control was of great significance for improving pregnancy complications and perinatal conditions. [8]Though numerous studies have explored the relationship between GDM and pregnancy outcomes, the vast majority of studies were focused on the risk of AMA for adverse pregnancy outcomes in AMA in both primiparous and perinatal mothers, [2,9,10] and few studies were reported in GDM women with advanced primiparous women.Our study aimed to examine the relationship between GDM and pregnancy outcomes in advanced primiparous women.

Study design and participants
The current study included 1076 eligible pregnant women from January 2020 to December 2022 in the Maternal and Child Health Hospital of Hubei Province.The inclusion criteria were as follows: primiparous women aged ≥35 years old; pregnant women with no history of prepregnancy diabetes; OGTT performed at 24-28 weeks; venous blood monitored during pregnancy and/or peripheral blood glucose; the data during pregnancy were complete.The exclusion criteria were as follows: the maternal age <35 years old; previous history of delivery, twin or multiple pregnancies.The diagnostic criteria of GDM as determined by 2-hours 75-grams OGTT were as follows: fasting blood glucose level of ≥5.1 mmol/L, 1-hour blood glucose level of ≥10.0 mmol/L, or 2-hours blood glucose level of ≥8.5 mmol/L.These advanced primiparous women were divided into the GDM group (n = 434) and the non-GDM group (n = 642).Subgroup analysis among GDM women was also conducted by the good or poor glycaemic control during pregnancy.Good glycaemic control was defined as fasting plasma glucose <5.3 mmol/L, 2-hours postload plasma glucose <6.7 mmol/L, and HbA1c <5.5%; otherwise, it was poor considered glycaemic control. [8]The 434 GDM women were further divided into women with good glycaemic control (n = 381) and women with poor glycaemic control (n = 53).The current study was approved by the Ethics Committee of our hospital (No. 2023IEC080).

Statistical analysis
Statistical analyses were performed using SPSS version 23.0 (SPSS, Chicago, IL, USA).Continuous data with the nonnormal distribution were presented as median (IQR) and analyzed using the Mann-Whitney U test.Categorical data were presented as n (%) and analyzed using the Chi-square test.The risk of adverse pregnancy outcomes was analyzed using the odds ratio (OR) and 95% confidence interval (CI) by multivariate logistic regression models.Adjustment was made for baseline characteristics of maternal age, height, weight, prepregnancy BMI, GWG, ART, and gravidity.P < .05 was considered statistically significant.

Results
A total of 1076 eligible advanced primiparous women were included in our study.All these women were divided into the GDM group (n = 434) and the non-GDM group (n = 642).Analysis of baseline characteristics demonstrated a significant difference in prepregnancy BMI (median, IQR: 22.27 [20.  1. Polyhydramnios was more frequently observed in the advanced primiparous women with GDM (5.76% vs 2.65%, P = .01).A significantly higher incidence rate of adverse pregnancy outcomes was found in advanced primiparous women with GDM, such as premature birth, low-birth weight, macrosomia, and NICU admission (all P < .05).Detailed information about the comparison of pregnancy outcomes was shown in Table 2.
The multivariate logistic regression models were built.After adjustment for baseline characteristics of maternal age, height, weight, prepregnancy BMI, GWG, ART, and gravidity, the ORs for the risk of adverse pregnancy outcomes according to GDM were presented in Table 3. GDM had almost twice the risk for developing polyhydramnios (adjusted OR: 1.94, 95% CI: 1.01-3.72,P = .04).Subgroup analysis was performed to explore the effect of glycaemic control on pregnancy outcomes (Table 4).Of the 434 advanced primiparous women with GDM, 381 had good glycaemic control, and 53 had poor glycaemic control.The poor glycaemic group showed a significantly higher incidence rate of polyhydramnios, hypertensive disorders of pregnancy, cesarean delivery, premature birth, low-birth weight, macrosomia, and NICU admission than the good glycaemic control group (all P < .05).

Discussion
Socio-economic development and assisted reproductive technologies have led to delays in childbearing.Age is an inherent risk factor in the development of metabolic diseases. [13]With the widespread use of glucose diagnostic monitoring technology and pregnancy checkups, the detection rate of gestational diabetes has increased to a certain degree.Many studies reported AMA and GDM were related to adverse pregnancy outcomes. [6,14]However, no research has addressed the association of GDM with pregnancy outcomes in advanced primiparous women.Thus, we investigated GDM and pregnancy outcomes in advanced primiparous women in the current study.Our findings demonstrated that GDM was an independent risk of developing polyhydramnios in advanced primiparous women.At the same time, good glycaemic control in diabetics advanced primiparous women could reduce adverse pregnancy outcomes.
Studies showed that the risk of developing GDM is higher in older pregnant women, and AMA (≥35 years) was a welldocumented and unmodifiable risk factor for GDM. [15]Obesity and inadequate GWG were other known risk factors for GDM. [16,17]The current study included 1076 advanced primiparous women and found the prepregnancy weight and BMI in the GDM group were much higher than those in the non-GDM group; due to metabolic changes and inactive lifestyle during pregnancy, especially the decrease in insulin sensitivity in late pregnancy, suggesting obese pregnant women with a higher risk of dyshomeostasis during pregnancy.The current study found the GWG was much lower in the GDM group than in the GDM group (median, IQR: 11.50 [8.0-15.0]vs 14.0 [11.0-17.0],P < .01).Similarly, a study from Spain also reported that GWG was lower in diabetic women (10.88 ± 6.46 vs 12.30 ± 5.42 kg; P = .013). [18]The current study also reported a larger proportion of advanced primiparous women with GDM had inadequate GWG (42.17%).
As is well-known, GDM is related to adverse pregnancy outcomes, such as hypertriglyceridemia, PROM, premature birth, postpartum hemorrhage, low-birth weight, macrosomia, fetal distress, etc. [19] The incidences of adverse pregnancy outcomes between the GDM group and non-GDM group in advanced primiparous women were also compared.The current study found the incidence of polyhydramnios, premature birth, lowbirth weight, macrosomia, and NICU admission was higher in the GDM group (all P < .05).Subsequently, a multiple logistic regression model was conducted to control potential confounders for adverse pregnancy outcomes based on GDM.Our results showed that GDM was an independent risk of developing polyhydramnios (adjusted OR = 1.94, 95% CI: 1.01-3.72).A prospective cohort study of 694 pregnant women in Ethiopia found a higher incidence of gestational hypertension, PROM, prenatal hemorrhage, and postpartum hemorrhage in pregnant women with GDM. [20]Polyhydramnios can result from a multifactorial etiology.Many fetal and maternal conditions, such as glycemic impairments, could lead to amniotic fluid abnormalities during pregnancy. [21]Excess glucose entered the fetus through the placenta when maternal blood glucose increased.The high levels of sugar entering the fetus through the placenta promoted hyperglycemia and hyperosmolar diuresis, which led to increased urinary excretion, excess maternal amniotic fluid, and the incidence of PROM and premature birth. [22]In contrast, this study found no significant difference in the incidence of PROM among the GDM group and non-GDM group.It may be explained by the cesarean section chosen as the preferred mode of delivery by more and more advanced primiparous women, avoiding the occurrence of PROM.Although polyhydramnios was associated with diabetes during pregnancy, [23] the association with the timing of the onset of GDM was not sure.More studies are needed to explore the potential effect of GDM on polyhydramnios.
To observe the effects of glycaemic control of GDM on pregnancy outcomes in advanced primiparous women, a subgroup analysis among the 434 women with GDM was conducted.There were 381 women with good glycaemic control and 53 women with poor glycaemic control.As expected, good glycaemic control reduced adverse pregnancy outcomes, such as polyhydramnios, hypertensive disorders of pregnancy, cesarean delivery, premature birth, low-birth weight, macrosomia, and NICU admission.Our study also highlighted the importance of blood glucose in primiparous women of advanced age.Lifestyle behavior change is essential to managing GDM for many women. [24]Lifestyle behavior change mainly includes dietary and exercise intervention.Table 3 The results for the odds ratios for the risk of adverse pregnancy outcomes according to GDM, after adjustment for baseline characteristics.The risk for adverse pregnancy outcomes was analyzed using the odds ratio (OR) and 95% confidence interval (CI) by multivariate logistic regression models.Adjustment was made for baseline characteristics of maternal age, height, weight, prepregnancy body mass index, gestational weight gain, assisted reproductive technology, and gravidity.CI = confidence interval, GDM = gestational diabetes mellitus, NICU = neonatal intensive care unit, OR = odds ratio, PROM = premature rupture of membrane.

OR
Although there is no consensus on which nutritional approach should be adopted for GDM, increasing evidence has reported that a low glycemic index diet was beneficial for diabetes in the past decade. [25]A meta-analysis by Li et al showed that exercise prescription for GDM patients could manage GDM and improve adverse pregnancy outcomes effectively. [26]Pregnant women with GDM are recommended to exercise at least twice a week for at least 20 to 50 minutes with at least moderate intensity. [27]owever, there are some limitations to be issued in this study.Considering it was a retrospective study in a single center, there may be unavoidable information bias and selection bias.The current study lacked adjustment for individualized maternal glycaemic control, which may also affect maternal and neonatal outcomes.Therefore, more studies are needed to examine the impact of glycaemic control on maternal and neonatal outcomes in advanced primiparous women.Medical institutions should take into account their management capabilities and the results of OGTT examinations and glucose monitoring in the later stages of gestational diabetes to stratify pregnant women, especially those with more severe glucose metabolism abnormalities, to improve their compliance and self-management capabilities to reduce the occurrence of adverse pregnancy outcomes and promote maternal and infant health.

Conclusion
Our findings supplemented the limited evidence of GDM in advanced primiparous women, providing valuable support for GDM Management in maternal women with AMA.GDM was an independent risk factor for developing polyhydramnios in diabetics advanced primiparous women.Good glycaemic control in diabetics advanced primiparous women could effectively reduce adverse pregnancy outcomes.It is necessary to identify high-risk individuals early and take preventive and intervention measures to reduce the risk of GDM and adverse pregnancy outcomes.

Table 4
Subgroup analysis was used to analyze the effect of glycaemic control of gestational diabetes mellitus on pregnancy outcomes in advanced primiparous women.

Variables
Good

a
Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, P.R. China.

Table 1
Comparison of baseline characteristics of advanced primiparous women with/without GDM.

Table 2
Comparison of pregnancy outcomes of advanced primiparous women with/without GDM.